Parkinson's Disease (PD) is one of the major progressive neurological disorders for which no preventative or long-term effective treatment strategies are available. Idiopathic PD is a multisystem disorder with a multifactorial etiology and diverse clinical phenotype. The risk of developing PD increases with age, and afflicted individuals are usually adults over 40. PD occurs in all parts of the world, and affects more than one million individuals in the United States alone.
PD is characterized by degeneration of dopaminergic neurons of the substantia nigra. The substantia nigra is a portion of the lower brain, or brain stem, that helps control voluntary movements. The shortage of dopamine in the brain caused by the loss of these neurons is believed to cause the observable disease symptoms.
The symptoms of PD may vary from patient to patient. The most common symptom is a paucity of movement: That is, rigidity characterized by an increased stiffness of voluntary skeletal muscles. Additional symptoms include resting tremor, bradykinesia (slowness of movement), poor balance, and problems walking. Common secondary symptoms include depression, sleep disturbance, dizziness, stooped posture, dementia, and problems with speech, breathing, and swallowing. The symptoms become progressively worse and ultimately result in death.
The primary cause of Parkinson's Disease is not known. Polymorphism in certain genes appears to be a risk factor, but there is no direct evidence for the causal relationship between polymorphism and increased risk of PD. Only a small percentage (<5%) of patients develop PD that may be linked to the currently known gene mutations (1). In familial PD, mutation in the synuclein gene is associated with the disease, but a direct role of this gene in degeneration of dopaminergic neurons remains to be established. Although mutations in the Parkin gene have been associated with autosomal recessive juvenile Parkinson's Disease, the role of this gene mutation in causing degeneration of dopaminergic neurons has not been defined. In idiopathic PD, epigenetic (mitochondria, membranes, protein modifications) rather than genetic events may be primary targets which, when impaired, initiate degeneration of dopaminergic neurons, eventually leading to cell death.
Although the nature of neurotoxins that cause degeneration in dopaminergic neurons in PD is not well understood, oxidative stress is one of the intermediary risk factors that could initiate and/or promote such degeneration. Therefore, supplementation with antioxidants may prevent or reduce the rate of PD progression. Supplementation with multiple antioxidants at appropriate doses is desirable because: various types of free radicals are produced in vivo, antioxidants vary in their ability to quench different free radicals, and cellular environments vary with respect to their lipid and aqueous phases. L-dihydroxyphenylalanine (L-dopa) is one of the agents used in the treatment of PD.
In addition to genome-wide association studies, which have identified polymorphisms that potentially confer susceptibility to PD (2), gene array surveys of the substantia nigra (SN) and other regions of the brain have provided some insights into the biological, cellular and molecular pathways implicated in PD (3-7).
There is a continuing need to identify genes and gene products that are associated with Parkinson's Disease or the progression of Parkinson's Disease, to provide means for screening, diagnosing, and evaluating Parkinson's Disease patients and patients suspected of having Parkinson's Disease. By identifying such genes and gene products, Parkinson's Disease treatments can be identified, evaluated, and may be selected for individualized care of PD patients.